Evidence map›Paper›PMID 42098862›Full record

ArticleCritical care (London, England)2026

EBV reactivation and immunoparalysis indicate a harmful immune endotype in sepsis.

K S Rosiewicz, M Anft, U Stervbo, S Skrzypczyk, S Kaliszczyk, B Koos, K Rump, H Nowak, M Unterberg, T H Westhoff and 10 more

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Article in Critical care (London, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

20 authors.

K S RosiewiczCenter for Translational Medicine, Medical Department 1, Marien Hospital Herne, University Hospitals of the Ruhr-University of Bochum, Hölkeskampring 40, 44625, Herne, Germany.
M AnftCenter for Translational Medicine, Medical Department 1, Marien Hospital Herne, University Hospitals of the Ruhr-University of Bochum, Hölkeskampring 40, 44625, Herne, Germany.
U StervboCenter for Translational Medicine, Medical Department 1, Marien Hospital Herne, University Hospitals of the Ruhr-University of Bochum, Hölkeskampring 40, 44625, Herne, Germany.
S SkrzypczykCenter for Translational Medicine, Medical Department 1, Marien Hospital Herne, University Hospitals of the Ruhr-University of Bochum, Hölkeskampring 40, 44625, Herne, Germany.
S KaliszczykCenter for Translational Medicine, Medical Department 1, Marien Hospital Herne, University Hospitals of the Ruhr-University of Bochum, Hölkeskampring 40, 44625, Herne, Germany.
B KoosKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Knappschaft Kliniken Universitätsklinikum Bochum GmbH, Ruhr Universität Bochum, In der Schornau 23-25, 44892, Bochum, Germany.
K RumpKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Knappschaft Kliniken Universitätsklinikum Bochum GmbH, Ruhr Universität Bochum, In der Schornau 23-25, 44892, Bochum, Germany.
H NowakKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Knappschaft Kliniken Universitätsklinikum Bochum GmbH, Ruhr Universität Bochum, In der Schornau 23-25, 44892, Bochum, Germany.
M UnterbergKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Knappschaft Kliniken Universitätsklinikum Bochum GmbH, Ruhr Universität Bochum, In der Schornau 23-25, 44892, Bochum, Germany.
T H WesthoffMarien Hospital Herne, University Hospitals of the Ruhr-University of Bochum, Medizinische Klinik 1, Hölkeskampring 40, 44625, Herne, Germany.
T BrennerDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, Hufelandtsr. 55, 45147, Essen, Germany.
M TrillingInstitute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
M Schmueck-HenneresseCenter for Regenerative Therapies, BCRT, Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
K WolkKlinik für Dermatologie, Venerologie und Allergologie, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Luisenstraße 2, 10117, Berlin, Germany.
R SabatKlinik für Dermatologie, Venerologie und Allergologie, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Luisenstraße 2, 10117, Berlin, Germany.
J GregoriusDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, Hufelandtsr. 55, 45147, Essen, Germany.
F WapplerKlinik für Anästhesiologie und operative Intensivmedizin, Klinikum Köln-Merheim, Ostmerheimer Str. 200, 51109, Köln, Germany.
A ZarbockKlinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Universitätsklinikum Münster, Albert-Schweitzer-Str. 33, 48149, Münster, Germany.
M AdamzikKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Knappschaft Kliniken Universitätsklinikum Bochum GmbH, Ruhr Universität Bochum, In der Schornau 23-25, 44892, Bochum, Germany.
N BabelCenter for Translational Medicine, Medical Department 1, Marien Hospital Herne, University Hospitals of the Ruhr-University of Bochum, Hölkeskampring 40, 44625, Herne, Germany. Nina.babel@charite.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSepsis is increasingly recognized as a highly dynamic immunological disorder in which hyperinflammation and anti-inflammatory processes occur simultaneously. The clinical phenotype depends on which arm predominates at a given time, resulting in an early phase that is typically dominated by hyperinflammation and a subsequent phase characterized by hypoinflammation, also referred to as immunoparalysis (IP). Epstein-Barr virus (EBV) reactivation has been associated with an immunosuppressive status. However, its interaction with IP and resulting immune phenotypes remains poorly defined so far. In this current study, we investigated the temporal dynamics of EBV reactivation and IP status, and assessed their impact on immune signatures and mortality in sepsis.

methodsIn this retrospective cohort of 124 intensive care unit (ICU) patients with sepsis, we performed analysis of EBV load by qPCR and analyzed the inflammatory stage by quantifying HLA-DR molecules on monocytes (mHLA-DR) using flow cytometry. Patients with < 5,000 mHLA-DR/monocyte were classified positive for immunoparalysis (IP+). Cytokine profiles and vital sign were analyzed in parallel. Patients were assigned to four sepsis groups based on EBV/IP status (EBV- IP-, EBV + IP-, EBV- IP+, EBV + IP+). Time-dependent Cox models (start-stop structure) were used to estimate hazard ratios (HR) for mortality, adjusted for age, sex and Sequential Organ Failure Assessment (SOFA) score. Cytokines and clinical markers were compared using Kruskal-Wallis and rank-based analyses.

resultsEBV positivity was associated with higher hazard of death (HR 3.30, 95% CI 1.24-8.81, p = 0.0009), while IP showed a similar but nonsignificant trend (HR 2.14, 95% CI 0.93-4.90, p = 0.073). The combined EBV + IP+ group exhibited the highest mortality (HR 7.23, 95% CI 2.24-23.3, p = 0.0009). This group also showed the strongest cytokine activation (IL-6, IL-8, IL-10, IL-17 A, IL-18, MCP-1) and lowest mHLA-DR expression, indicating a mixed hyperinflammatory and immunosuppressed phenotype. In contrast, EBV- IP- patients displayed the most immunocompetent baseline profile.

conclusionOur preliminary findings suggest that EBV reactivation superimposed on immunoparalysis is associated with a harmful sepsis endotype combining excessive cytokine activity with impaired monocyte function. Further studies are needed to evaluate if the dynamic monitoring of EBV DNA and mHLA-DR expression may enable early identification of patients at highest risk and guide targeted immunomodulatory or antiviral interventions.

Indexed as

Epstein-Barr Virus InfectionsHerpesvirus 4, HumanSepsisVirus ActivationAgedCohort StudiesCytokinesFemaleHumansIntensive Care UnitsMaleMiddle AgedProportional Hazards ModelsRetrospective StudiesCytokines

Identifiers

PMID42098862
PMCPMC13154855

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.